The present invention relates to an active ingredient obtained from a gastropod (e.g., a snail) for use in therapeutic and cosmetic compositions. The compositions are applied to the skin or various mucous membranes.
Products derived from snails have been used in various medical products and processes. .beta.-Glucuronidase obtained from crop fluid of the snail Helix pomatia has found use in a method for detecting morphine and its analogues, as well as enzymatic studies involving the metabolism of steroids (see U.S. Pat. No. 4,473,640 issued to J. D. Combie et al.). A Fascioliasis vaccine, particularly for bovine administration, is prepared from Lymnaea natalensis (see U.S. Pat. No. 4,314,992 issued to P. K. Bitakaramire). A polysaccharide hydrolyzing enzyme produced by a snail is used to treat yeast cells so that the walls disintegrate (see U.S. Pat. No. 3,889,006 issued to T. Nagasawa et al). Serum proteins such as hemocyanin from the Keyhole limpet (a marine gastropod mollusk) have been used to modify the peptides administered to primate animals to control biological activity attributable to chorionic gonadotropin (see U.S. Pat. No. 4,855,285 issued to V. C. Stevens).
U.S. Pat. No. 3,8815,012 (issued to Tschesche et al.) discloses the preparation of a protease-inhibiting substance (an iso-inhibitor) from homogenized edible snails of the genus Helix and family Helicidae (e.g., Helix pomatia).
The iso-inhibitor of the '012 patent is a chemically treated product derived from dead edible snails from a specific genus and family. The homogenized mixture used to produce the iso-inhibitors contains the blood, muscle, kidney, lung, and excrement of the edible snail. With a dead animal, such as the frozen and shelled snails used in the '012 composition, the starting product derived contains the product from the last biological reaction of that animal. Also, the product may contain toxic substances from the snail muscle and pathogenic viruses from the excrement.
The iso-inhibitors are prepared by: (a) homogenizing (i.e., crushing) the shelled frozen snails; (b) separating the resulting homogenate into a precipitate and a supernatant liquid (generally the separation is carried out by centrifuging at about 12,000 rpm (24,000 G) for 60 minutes); (c) mixing the supernatant liquid with ammonium sulfate up to 63% of the saturation concentration to precipitate the protease--inhibiting substance; and (d) optionally fractionating the substance by gel fractionation and selecting the most active fraction(s) or optionally fractionating the substance on a cation exchange resin to obtain a plurality of fractions containing a different iso-inhibitor.
The medical indications for the '012 composition are negative and diverse. They include injectable aqueous solutions containing the iso-inhibitors for use in the treatment of thrombotic or hemorrhagic conditions including acute pancreatitis, obstructive thrombus, nasal plugging, stopping bleeding in the sinus maxillas, esophagus varices in cirrhosis of the liver, and uterus carcinoma. One of the three prophylactic haemostyptic uses suggested is reduction of radiation damage in irradiation of malignant growths (i.e., cancer tumors).
Radiodermatitis (i.e., dermatitis resulting from overexposure to sources of radiant energy such as x-rays, gamma radiation or like radiation) is one of the most annoying complications in the treatment of neoplastic diseases and can lead to the suspension of treatment. It is also the feared occupational disease of medical practitioners who carry out the radiation treatments and of people working in nuclear plants. One of the most serious threats is the possible development of cancer from such exposure. Burns of all types are also one of the most difficult conditions to treat.
Treatments for radiodermatitis are discussed in the article "A New Substance In The Treatment Of Radiodermatitis, Particularly of Neoplastic Patients. Radiobiological and Therapeutic Factors" by Dr. Rafael Abad, Acta Oncological, VI, No. 1 (January-June 1967). The treatments include surgical treatments, physical treatments such as the use of ultraviolet, infrared, and red spectrum rays, ultrasonics, diathermy, and radar, and pharmacological treatments using inorganic, organic or biological products.
The physical treatments have little value except as a supplement to another primary therapy and are not recommended for cases occurring in an area with neoplastic processes. The danger of necrosis must be seriously considered before any physical treatments are employed. Infrared and red spectrum rays are not used because they increase erythema. Ultraviolet radiation was commonly used but is no longer used, even though it can lower pain at the lowest doses, because it has no prophylactic effect. The use of radar as an anti-inflammatory agent at very weak doses is effective; however, it can cause vascular complications like permeability and sweating.
Many pharmacological treatments have been tried. These include oral administration of large amounts of potassium iodide, local administration of acidified hydrogen peroxide to form nascent iodine in situ, and topical treatments with paraffin, zinc stearate, zinc oxide, animal fats (e.g., lanolin), petroleum jelly, and salves containing the juice of the aloe vera plant. These treatments are non-specific and most act as a mere excipient. Topical treatments often include anesthetics to relieve the pain, antihistamines to relieve the itch and redness, and vegetable materials such as chlorophyll. Other ingredients are used to increase penetration by means of hyaluronidase. Vitamin H, Vitamins A and D (halibut ointment), and pantothenic acid alone or mixed in a lyophilized mixture with trypsin have also been used although they are not curative. Sulfide-containing amino acids are important as radioprotectors and regenerators of radiolesions. Cysteine and methionine have been used both internally and topically. Various hormones have been used, including insulin, adrenalin, thyroid, female hormones, and heparin (topically). The use of insulin and adrenalin as radioprotectors is undesirable since they increase sensitivity. The use of cortisone (both topically and internally) is important. Substances such as nitrogenated mustards and chloroquine have also been used unsuccessfully.
The treatment of burns produced by ionizing radiations, chemical agents (e.g., mustard gas or similar agents used in chemical warfare), and thermal agents presents similar problems. The products used to treat the burns are non-specific and most act as mere excipients. They include blastostimulins, chymotrypsin, trypsin, cortisone, pantothenic acid, and vitamins.
Ionizing radiation is more likely to cause more devitalization, whereas thermal and chemical burns are more likely to cause necrosis. Repeated exposure to ultraviolet radiation is more likely to cause cancer (similar to the cancers caused by low and repeated doses of ionizing radiation). With all types of burns, skin or mucous cancer can develop.
The above treatments have not, however, been satisfactory. There is therefore a need for an effective therapeutic composition, particularly a composition which decreases local reactivity and protects the skin or mucous membrane, mitigates pain, favors tissue regeneration, eliminates cellular detritus, and prevents infection. Specifically, there is a need for a therapeutic composition which is both a radioprotector (i.e., it protects against radiodermatitis) and a restorative. There is also a need for a therapeutic composition which is effective in the treatment of other types of burns, particularly injuries to skin and mucous membranes caused by exposure to chemical agents, and which can prevent skin cancer due to exposure to ultraviolet light. There is also a need for a composition for use in the treatment of abrasions, rashes, wounds, varicose ulcers and the like. There is also a need for a composition for use in the treatment of wrinkled skin or skin with stretch marks.
Many cosmetic treatments have been tried. These include treatments with vitamins, embryonic, and placental extracts which either place water or lipids on the skin.
The above treatments have not been satisfactory. There is therefore a need for a regenerative treatment that acts as a biological coating.